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Salivary Osteopontin as a Potential Biomarker for Oral Mucositis.

Osteopontin (OPN), a multifunctional phosphoglycoprotein also presents in saliva, plays a crucial role in tumour progression, inflammation and mucosal protection. Mucosal barrier injury due to high-dose conditioning regimen administered during autologous and allogeneic peripheral stem cell transplantation (APSCT) has neither efficient therapy nor established biomarkers. Our aim was to assess the biomarker role of OPN during APSCT, with primary focus on oral mucositis (OM). Serum and salivary OPN levels were determined by ELISA in 10 patients during APSCT at four stages of transplantation (day

Peripheral inflammatory T cell subsets are effective predictive factors in the development of heterotopic ossification after posttraumatic elbow surgery.

Heterotopic ossification refers to the pathological formation of extra-skeletal bone. It is a common complication of trauma or surgery that can cause disability and has no definitive cure. Furthermore, the mechanisms underlying chronic inflammation during ossification remain unclear. Therefore, this study aimed to elucidate the systemic immune microenvironment status of heterotopic ossification and identify biomarkers of therapeutic efficacy and recurrence. A combination of stereoarthrolysis with prophylactic radiotherapy and non-steroidal anti-inflammatory drugs was used to treat patients wit

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA-mRNA Interaction Involvement.

Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA-mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viabi

Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: in vitro and in vivo anti-tumor activity.

Multiple myeloma (MM) cells induce relevant angiogenic effects within the human bone marrow milieu (huBMM) by the aberrant expression of angiogenic factors. Hypoxia triggers angiogenic events within the huBMM and the transcription factor hypoxia-inducible factor-1α (HIF-1α) is over-expressed by MM cells. Since synthetic miR-199a-5p mimics negatively regulates HIF-1α, we here investigated a miRNA-based therapeutic strategy against hypoxic MM cells. We indeed found that enforced expression of miR-199a-5p led to down-modulated expression of HIF-1α as well as of other pro-angiogenic factors such a

Диет модернизирует терапевтическое воздействие диметилфумарата, поддерживаемого иммунометаболическим нейтрофильным рецептором HCAR2.

Монометилфумарат (ММФ) и его пронаркодиметилфумарат (ДМП) в настоящее время являются наиболее широко используемыми агентами для лечения множественных склерозов (МС). Однако не все пациенты получают помощь от ДМФ. Мы предположили, что переменная реакция пациентов может быть связана с их питанием. В поддержку этой гипотезы мыши, подвергшиеся экспериментальному аутоиммунальному энцефаломиэлиту (EAE), являющемуся моделью MS, не пользовались лечением DMF при питании богатой лауричной кислотой диетой. В противоположность этому, мыши на нормальном питании чау (NC) и даже мыши на рационе с высоким сод

TGFα контролирует контрольно-пропускные пункты в СНК, проживающих в них, и внедряет иммунные клетки в целях содействия урегулированию проблемы воспаления.

После острых повреждений в центральной нервной системе (КНС) взаимодействие микроглий, астроцитов и проникновение иммунных клеток принимает решение об их разрешении или хронизации. Однако этот перекрестный разговор CNS-интригинальный характерен плохо. Анализируя образцы цереброспайнальной жидкости (CSF) пациентов с множественным склерозом (MS), а также образцы CNS женских мышей с экспериментальным аутоиммунным энцефаломиелитом (EAE), т.е. С помощью механистических исследований in vitro, в парадигмах лечения vivo, последовательности scRNA, моделей генетического возмущения CRISPR-Cas9 и MRI в мо

Image-based drug screen identifies HDAC inhibitors as novel Golgi disruptors synergizing with JQ1.

The Golgi apparatus is increasingly recognized as a major hub for cellular signaling and is involved in numerous pathologies, including neurodegenerative diseases and cancer. The study of Golgi stress-induced signaling pathways relies on the selectivity of the available tool compounds of which currently only a few are known. To discover novel Golgi-fragmenting agents, transcriptomic profiles of cells treated with brefeldin A, golgicide A, or monensin were generated and compared with a database of gene expression profiles from cells treated with other bioactive small molecules. In parallel, a p

Exosomes Derived from Pancreatic Cancer Cells Induce Osteoclast Differentiation Through the miR125a-5p/TNFRSF1B Pathway.

BackgroundPancreatic cancer (PC) was regarded as the 4th principal cause of cancer-related fatalities in the United States and patients usually suffered from severe nutrition deficiency, muscle wasting, as well as bone loss. In our previous research, we have found that PC-derived exosomes potentially initiate insulin resistance in skeletal muscle cells. However, the role of exosomes in the PC-related bone loss remains unknown.MethodsThe effect of PC-derived exosomes on the osteoclast differentiation and femoral bone structure in the orthotopic xenograft mouse model were investigated. MiRNA exp

The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells.

The rapid emergence of resistance limits the application of proteasome inhibitors against solid tumors, despite their effectiveness in the treatment of hematological malignancies. Resistant phenotypes are complex and multifaceted, and, thus, the mechanisms involved have not been adequately described. In this study, a Bortezomib-resistant prostate cancer cell line is created by using the PC-3 cell as a prostate carcinoma model of high metastatic potential. The main biochemical differences and adaptations exhibited by the resistant cells revolve around apoptosis evasion, autophagy induction (fun

Intrinsic retinoic acid synthesis is required for oligodendrocyte progenitor expansion during CNS remyelination.

Myelin regeneration (remyelination) in the CNS depends on the recruitment, proliferation and differentiation of oligodendrocyte precursor cells (OPCs) at demyelinated lesions. However, despite the presence of OPCs, very few oligodendrocytes and myelin are regenerated in chronic multiple sclerosis (MS) lesions for reasons that remain poorly understood. Here, using a spontaneous remyelination model in mice, we found that retinaldehyde dehydrogenase 2 (Raldh2), a rate-limiting enzyme for retinoic acid (RA) synthesis, is upregulated in OPCs and in a subpopulation of microglia/macrophages during re

CBD promotes antitumor activity by modulating tumor immune microenvironment in HPV associated head and neck squamous cell carcinoma.

IntroductionMarijuana use is associated with HPV-positive head and neck squamous cell carcinoma (HNSCC). However, cannabinoid use continues to increase in the US general population for recreational purposes as well as in cancer patients for palliative care. In this study, we explored the role of cannabidiol (CBD) in promoting anti-tumor activity by modulating immune response in HPV-positive HNSCC by using pre-clinical models.MethodsThe anti-proliferative effect of CBD on HPV-positive HNSCC cells was evaluated through BrdU, apoptosis and migration analyses, followed by western blot analysis to

Selegiline induces neuroprotection via PGC-1α/Nrf2 gene upregulation in H2O2 -treated hippocampal-derived neural stem/progenitor cells.

Oxidative stress mediated by reactive oxygen species (ROS) is a major contributor to the pathogenesis of neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, multiple sclerosis, and amyotrophic lateral sclerosis. Selegiline, a monoamine oxidase B inhibitor, has been reported to exert neuroprotective effects, although its precise cytoprotective mechanisms remain unclear. In this study, we investigated the effects of selegiline on apoptosis, necrosis, and cell survival in hydrogen peroxide (H₂O₂)-treated hippocampal-derived neural stem/progenitor cells (HD-NSPCs) in vitr

Artificial Neural Networks Coupled with MALDI-TOF MS Serum Fingerprinting To Classify and Diagnose Pathological Pain Subtypes in Preclinical Models.

Pathological pain subtypes can be classified as either neuropathic pain, caused by a somatosensory nervous system lesion or disease, or nociplastic pain, which develops without evidence of somatosensory system damage. Since there is no gold standard for the diagnosis of pathological pain subtypes, the proper classification of individual patients is currently an unmet challenge for clinicians. While the determination of specific biomarkers for each condition by current biochemical techniques is a complex task, the use of multimolecular techniques, such as matrix-assisted laser desorption/ioniza

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… Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice. Sci. Rep. 2018, 8, 3873. 10.1038/s41598-018-22217-9. Bagó-Mas A.; Korimová A.; Deulofeu M.; Verdú E.; Fiol N.; Svobodová V.; Dubový P.; Boadas-Vaello P. … Repeated Sigma-1 Receptor Antagonist MR309 Administration Modulates Central Neuropathic Pain Development After Spinal Cord Injury in Mice. Front. Pharmacol. 2019, 10, 222. 10.3389/fphar.2019.00222. Boccard J.; Rudaz S.. Mass Spectrometry Metabolomic Data Handling for Biomarker Discovery. …

Benzyl isothiocyanate suppresses development of thyroid carcinoma by regulating both autophagy and apoptosis pathway.

Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer, characterized by rapid growth and invasion and poor prognosis. Due to its rarity and aggressive nature, ATC is a difficult condition to treat, thus knowledge of the mechanisms underlying its progression represents important research challenges. Benzyl isothiocyanate (BITC) is a natural compound that has shown promising anticancer properties. The aim of this study was to evaluate the antitumor effect of BITC in ATC, highlighting signaling pathways involved in BITC mechanism of action. This work included in vitro a

Anticancer effect of minor phytocannabinoids in preclinical models of multiple myeloma.

Multiple myeloma (MM) is a blood cancer caused by uncontrolled growth of clonal plasmacells. Bone disease is responsible for the severe complications of MM and is caused by myeloma cells infiltrating the bone marrow and inducing osteoclast activation. To date, no treatment for MM is truly curative since patients relapse and become refractory to all drug classes. Cannabinoids are already used as palliative in cancer patients. Furthermore, their proper anticancer effect was demonstrated in many cancer models in vitro, in vivo, and in clinical trials. Anyway, few information was reported on the e

Сипонимод поддерживает воспоминание в неподдерживающей среде.

Воспаление, характерное для множественных повреждений склероза (MS), приводит к функциональным повреждениям и постепенной потере аксона с течением времени. Хотя, как считается, ремилеляция защищает аксоны, внутренние регенерационные процессы часто являются неполными или полностью неэффективными у многих пациентов с синдромом MS. Хотя точные причины провала воспоминаний остаются неясными, неоднократное обезвоживание в ранее затронутых районах с белыми телами является признанным фактором, способствующим этому. В одном из предыдущих исследований мы продемонстрировали, что модификатор Siпонimod с

Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes.

Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with parado

Распространение эпсилонного токсина Clostridium Perfringens изолируется среди пациентов с множественным склерозом и расстройством спектра нейромиелита в Иране.

Клостридий перфрингенс эпсилон токсин (ETX) является мощным нейротоксином, который пересекает мозговой барьер (BBB) и который, как было предложено, связан с демиелинизирующими расстройствами CNS. Здесь мы изучили распространенность C. перфрингенов и антиETX иммуноглобулина G (IgG) и иммуноглобулина M (IgM) в стуле и сере пациентов с множественным склерозом (MS) и спектральным расстройством нейромиелита (NMOSD) по сравнению со здоровым контролем. МЕТОДЫ: В период с сентября 2019 года по июнь 2020 года было собрано 43 образца стула и 43 образца серы из MS (n = 33) и NMOSD (n = 10) пациентов, а т

Роль CD20+T клеток в раннем множественном склерозе.

Релапсирующий множественный склероз (RRMS) — хроническое иммунное заболевание центральной нервной системы (CNS), характеризующееся эпизодическими рецидивами неврологических симптомов. Ранняя диагностика и лечение пациентов имеют ключевое значение для предотвращения рецидивов и необратимого ущерба для ЦНС. Вместе с тем развитие методов лечения, ориентированных на ранние МЗ, сдерживается отсутствием знаний о патогенезе ранней МЗ. В RRMS повреждение нервной ткани вызывается иммунными клетками CNS, в том числе Т. Таким образом, цель этого исследования заключалась в изучении ранних случаев инфильтр

Frentizole, a Nontoxic Immunosuppressive Drug, and Its Analogs Display Antitumor Activity via Tubulin Inhibition.

Antimitotic agents are one of the more successful types of anticancer drugs, but they suffer from toxicity and resistance. The application of approved drugs to new indications (i.e., drug repurposing) is a promising strategy for the development of new drugs. It relies on finding pattern similarities: drug effects to other drugs or conditions, similar toxicities, or structural similarity. Here, we recursively searched a database of approved drugs for structural similarity to several antimitotic agents binding to a specific site of tubulin, with the expectation of finding structures that could f